This application will examine the genetic factors that influence the development of chronic obstructive pulmonary disease (COPD) in Hispanics, a minority group at high risk for the disease. To this end, we will concentrate on a genetically isolated Hispanic population with a high prevalence of COPD living in the Central Valley of Costa Rica. To identify regions of the genome likely to contain genetic determinants of COPD-related phenotypes in this population, we will utilize a study design that entails collection of phenotypic and genotypic data on 30 large families of probands with moderate to severe COPD that have multiple individuals affected with smoking-related airflow obstruction, comprising 900 individuals from descendants of the Costa Rican Central Valley founder population. We will conduct a genome scan on these large pedigrees using short-tandem repeat (STR) markers and perform linkage analysis of six COPDrelated phenotypes: chronic bronchitis; airflow obstruction; FEV1; FEV1/FVC; bronchodilator responsiveness; and total serum IgE. Within genomic regions demonstrating linkage to COPD-related phenotypes in the genome scan, we will genotype narrowly spaced STR markers and test for linkage between these markers and COPD-related phenotypes. Within selected genomic regions, we will then test for association between single nucleotide polymorphisms (SNPs) in candidate genes and COPD-related phenotypes. By utilizing a family-based study design with a large sample size in a genetically isolated population, we should be able to address an important yet unstudied problem: the genetic influences on the expression of the COPD phenotype in Hispanics. This application will greatly contribute to our understanding of the pathogenesis of COPD in general, and among Hispanics in particular.